A pathway for mitotic chromosome formation

被引:481
作者
Gibcus, Johan H. [1 ]
Samejima, Kumiko [2 ]
Goloborodko, Anton [3 ,4 ]
Samejima, Itaru [2 ]
Naumova, Natalia [1 ]
Nuebler, Johannes [3 ,4 ]
Kanemaki, Masato T. [5 ,6 ]
Xie, Linfeng [7 ]
Paulson, James R. [7 ]
Earnshaw, William C. [2 ]
Mirny, Leonid A. [3 ,4 ]
Dekker, Job [1 ,8 ]
机构
[1] Univ Massachusetts, Dept Biochem & Mol Pharmacol, Program Syst Biol, Med Sch, 368 Plantation St, Worcester, MA 01605 USA
[2] Univ Edinburgh, Wellcome Ctr Cell Biol, Kings Bldg, Edinburgh EH9 3BF, Midlothian, Scotland
[3] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[4] MIT, Dept Phys, Cambridge, MA 02139 USA
[5] Res Org Informat & Syst, Div Mol Cell Engn, Natl Inst Genet, Yata 1111, Mishima, Shizuoka 4118540, Japan
[6] SOKENDAI, Dept Genet, Mishima, Shizuoka 4118540, Japan
[7] Univ Wisconsin, Dept Chem, 800 Algoma Blvd, Oshkosh, WI 54901 USA
[8] Univ Massachusetts, Howard Hughes Med Inst, Med Sch, 368 Plantation St, Worcester, MA 01605 USA
基金
日本学术振兴会; 英国惠康基金; 美国国家科学基金会;
关键词
SISTER-CHROMATID RESOLUTION; CONDENSIN-I; METAPHASE CHROMOSOMES; VERTEBRATE CELLS; TOPOISOMERASE-II; SCAFFOLD ATTACHMENT; CHROMOKINESIN KIF4A; MAMMALIAN-CELLS; LOOP EXTRUSION; HUMAN GENOME;
D O I
10.1126/science.aao6135
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, similar to 80-kb inner loops are nested within similar to 400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold. The size of helical turns progressively increases to similar to 12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.
引用
收藏
页码:652 / +
页数:13
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